The overall aim of this project is to define the biochemical mechanisms responsible for the neurological abnormalities induced by hypoglycemia. There are two specific aims of the project: (1) to define what changes in metabolic products of glucose metabolism in brain are pathogenetically important in the production of hypoglycemic seizures and coma and (2) to define the neurochemical processes associated with and/or responsible for the production of irreversible functional and morphological changes induced by hypoglycemia. Mice and rats will be used for all studies. Changes in CNS levels of glycolytic and citric acid cycle intermediates and other selected substances will be measured in experimental animals rendered hypoglycemic and in those recovering from hypoglycemia. Concomitant functional and morphological changes will also be monitored and correlated with biochemical observations. Currently available biochemical methods and techniques which permit the preservation and measurement of labile and stable constituents in extremely small tissue samples, and even in single cells, will be used in these studies. A newly-devised method for performing electroencephalography on mice will also be utilized. Morphological examination will be performed at the light-microscopic level. Achievement of the aims of this project will lead to a definition and understanding of the neurochemical mechanisms of hypoglycemic seizures and coma. This, in turn, will provide a more complete understanding of epilepsy and coma in general and may lead to better diagnosis and treatment of these conditions.